Our aim is to determine the nature and magnitude of allele variation in genes coding for different types of polypeptides and to understand the adaptive significance of this variation. For this purpose, we have been studying the extent and magnitude of genetically determined variations that occur in the structure and activities of various enzymes. Distinctions among structurally different enzymes coded by alleles of a gene are made by various methods such as electrophoresis in different buffers of different molarities and pH and in gels with varying acrylamide concentrations; isoelectric focussing; denaturation with heat, urea, guanidine and pH; quantitative study of enzyme activity in the gels; kinetic studies; relative electrophoretic position and the amount of hybrid enzymes; and electrophoresis after treatment of crude extracts with various sulfhydryl reagents. We will study the variations of alleles in the esterase-5, xanthine dehydrogenase and hexokinase loci of Drosophila pseudoobscura by these methods. Polymorphism in ribosomal proteins of D. pseudoobscura will also be studied. Experiments for determining the adaptive significance of allele variation will be performed in Saccharomyces cerevisiae. BIBLIOGRAPHIC REFERENCES: Prakash, S. and M. Levitan. 1974. Association of alleles of the malic dehydrogenase locus with a pericentric inversion in Drosophila robusta. Genetics 77: 565-568. Prakash, S. 1974. Gene differences between the sex ratio and standard gene arrangements of the X chromosome and linkage disequilibrium between loci in the standard gene arrangement of the X chromosome in Drosophila pseudoobscura. Genetics 77: 795-804.